Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.publishedVersio

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose: Thrombocytopenia (platelet count &lt; 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic

The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment

The fibrinolytic system is a key player in keeping the haemostatic balance, and changes in fibrinolytic capacity can lead to both bleeding-related and thrombosis-related disorders. Our knowledge of the fibrinolytic system has expanded immensely during the last 75 years. From the first successful use of thrombolysis in myocardial infarction in the 1960s, thrombolytic therapy is now widely implemented and has reformed treatment in vascular medicine, especially ischemic stroke, while antifibrinolytic agents are used routinely in the prevention and treatment of major bleeding worldwide. Despite this, this research field still holds unanswered questions. Accurate and timely laboratory diagnosis of disturbed fibrinolysis in the clinical setting remains a challenge. Furthermore, despite growing evidence that hypofibrinolysis plays a central role in, e.g., sepsis-related coagulopathy, coronary artery disease, and venous thromboembolism, there is currently no approved treatment of hypofibrinolysis in these settings. The present review provides an overview of the fibrinolytic system and history of its discovery; measurement methods; clinical relevance of the fibrinolytic system in diagnosis and treatment; and points to future directions for research

In vitro effect of dalteparin and argatroban on hemostasis in critically ill sepsis patients with new-onset thrombocytopenia

Thrombocytopenia is common among critically ill sepsis patients, while they also hold an increased risk for thromboembolic events. Thus, the choice of anticoagulant prophylaxis for this patient population is challenging. We investigated the in vitro effect of low-molecular-weight heparin (dalteparin) and direct thrombin inhibitor (argatroban) on the hemostasis in blood from sepsis patients with new-onset thrombocytopenia. Thrombocytopenia was defined as a platelet count drop of ≥30% and/or from >100x109/L to 30-100x109/L within 24 hours prior to inclusion. We included five healthy individuals and ten patients. Analysis of thrombin generation (Calibrated Automated Thrombogram), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex levels, and thromboelastometry (ROTEM®) were performed. Based on dose-response-relationships investigated in healthy blood, patient samples were spiked with prophylactic (0.25 IU/mL) and therapeutic (0.75 IU/mL) dalteparin and low (0.25 µg/mL) and high (0.50 µg/mL) argatroban concentrations, each with a sample without anticoagulant. In patients, the endogenous thrombin potential was markedly lower in therapeutic dalteparin samples than in samples without anticoagulant [median (range): 29 (0-388) vs. 795 (98-2121) nM×min]. In high argatroban concentration samples, thrombin lag time was longer than in samples without anticoagulant [median (range): 15.5 (10.5-20.2) vs. 5.3 (2.8-7.3) min]. Dalteparin and argatroban both increased clotting time but did not affect maximum clot firmness in the ROTEM INTEM® assay. Six patients had elevated TAT and eight patients had elevated F1+2. In conclusion, dalteparin mainly affected the amount of thrombin generated and argatroban delayed clot initiation in critically ill sepsis patients with new-onset thrombocytopenia. Neither anticoagulant affected clot strength

Effect of remote ischemic preconditioning on hemostasis and fibrinolysis in head and neck cancer surgery: A randomized controlled trial.

IntroductionThe aim of this randomized controlled trial was to investigate if remote ischemic preconditioning (RIPC) reduced platelet aggregation and increased fibrinolysis in cancer patients undergoing surgery and thereby reduced the risk of thrombosis.Materials and methodsHead and neck cancer patients undergoing tumor resection and microsurgical reconstruction were randomized 1:1 to RIPC or sham intervention. RIPC was administered intraoperatively with an inflatable tourniquet by four cycles of 5-min upper extremity occlusion and 5-min reperfusion. The primary endpoint was collagen-induced platelet aggregation measured with Multiplate as area-under-the-curve on the first postoperative day. Secondary endpoints were markers of primary hemostasis, secondary hemostasis, and fibrinolysis. Clinical data on thromboembolic and bleeding complications were prospectively collected at 30-day follow-up. An intention-to-treat analysis was performed.ResultsSixty patients were randomized to RIPC (n = 30) or sham intervention (n = 30). No patients were lost to follow-up. The relative mean [95% confidence interval] collagen-induced platelet aggregation was 1.26 [1.11;1.40] in the RIPC group and 1.17 [1.07;1.27] in the sham group on the first postoperative day reported as ratios compared with baseline (P = 0.30). Median (interquartile range) 50% fibrin clot lysis time was 517 (417-660) sec in the RIPC group and 614 (468-779) sec in the sham group (P = 0.25). The postoperative pulmonary embolism rate did not differ between groups (P = 1.0).ConclusionsRIPC did not influence hemostasis and fibrinolysis in head and neck cancer patients undergoing surgery. RIPC did not reduce the rate of thromboembolic complications

Bleeding patients on extracorporeal membrane oxygenation have reduced platelet aggregation and plasma fibrinogen: a longitudinal observational study

Abstract This study investigated changes in coagulation and associations with occurrence of bleeding and thrombosis during extracorporeal membrane oxygenation (ECMO) therapy. The study included 100 adult ECMO-patients. Standard coagulation parameters, platelet aggregation and thromboelastometry (ROTEM®) were compared with healthy controls. Data on bleeding and thrombosis were collected until recovery or death. Mortality data were collected 30 days after weaning from ECMO. During ECMO therapy, 53 patients experienced at least one moderate or major bleed. Among these, 42 (79%) patients experienced the first bleeding on day 1 or 2. Platelet aggregation and ROTEM® revealed a hypocoagulable state in ECMO patients when compared with healthy controls. Patients bleeding on day 1 or 2, had lower platelet count (p = 0.04), poorer platelet aggregation and lower levels of fibrinogen (p < 0.01) than patients not bleeding on day 1 or 2. Further, ROTEM® clot propagation was reduced in bleeding patients (p < 0.001). Mortality was higher among bleeding patients than patients not bleeding on day 1 or 2 (67% versus 34%, p < 0.01). Congruity existed between ROTEM® measurements and standard coagulation assays, but plasma fibrinogen had a stronger association with bleeding than ROTEM® measurements. The present study does not support ROTEM® analysis as a routine part of coagulation monitoring during ECMO therapy